Institute for Clinical and Economic Review Publishes Final Evidence Report on Treatments for Paroxysmal Nocturnal Hemoglobinuria

— Independent appraisal committee voted that current evidence is not adequate to demonstrate a net health benefit for iptacopan over C5 inhibitor; committee voted that the evidence is adequate to demonstrate a net health benefit for add-on danicopan compared to C5 inhibitor alone —

BOSTON, March 13, 2024 – The Institute for Clinical and Economic Review (ICER) today released a Final Evidence Report assessing the comparative clinical effectiveness and value of iptacopan (Fabhalta, Novartis) and danicopan (Voydeya, Alexion Pharmaceuticals) for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). ICER’s report on these therapies was the subject of the February 2024 public meeting of the of the CTAF, one of ICER’s three independent evidence appraisal committees.

Downloads: Final Evidence Report | Report-at-a-Glance | Policy Recommendations

The independent appraisal committee voted that the current evidence is not adequate to demonstrate a net health benefit for iptacopan over a C5 inhibitor, although use in treatment-experienced patients with clinically significant extravascular hemolysis received more favorable votes. The committee also found that at current pricing, iptacopan represents “low” long-term value for money. Furthermore, the committee voted that the evidence is adequate to demonstrate a net health benefit for add-on danicopan compared to continuing C5 inhibitor alone in treatment-experienced patients on a stable C5 Inhibitor regimen with clinically significant extravascular hemolysis. Danicopan’s price is not yet known; however, ICER analyses suggest danicopan would achieve common thresholds for cost-effectiveness if priced between $12,300 to $13,100.   

“PNH is a rare, acquired blood disorder that primarily manifests in fatigue, and if severe, requires lifelong dependence on blood transfusions,” said ICER’s Vice President of Research, Foluso Agboola, MBBS, MPH. “Iptacopan (as an alternative to C5 inhibitor therapy) and danicopan (as an add-on to a C5 inhibitor) are promising new oral options for PNH patients. As indicated by the votes from the independent appraisal committee, the current evidence was judged more favorably for add-on danicopan in treatment-experienced PNH patients with anemia; however, there are still uncertainties around the long-term benefits of both therapies. The discussion during the public meeting highlighted the impact of high costs associated with C5 inhibitors – the current standard of care for PNH – on accessibility and affordability, and its effect on the pricing of new PNH therapies.”

ICER’s Virtual Public Meeting: Voting Results on Clinical Effectiveness and Contextual Considerations

ICER assessed, and the independent appraisal committee voted on, the evidence of iptacopan for individuals with treatment-naïve PNH:

A majority of panelists (12-1) found that current evidence is not adequate to demonstrate a net health benefit for iptacopan when compared to C5 inhibitor therapies.

For treatment-experienced individuals on a stable C5 Inhibitor regimen with clinically significant extravascular hemolysis:

A slight majority of panelists (7-6) found that current evidence is not adequate to demonstrate a net health benefit for switching to iptacopan when compared to continuing a C5 inhibitor.
A majority of panelists (12-1) found that current evidence is not adequate to demonstrate a net health benefit for switching to iptacopan when compared to continuing pegcetacoplan.
A majority of panelists (10-3) found that current evidence is adequate to demonstrate a net health benefit for adding danicopan to a C5 inhibitor when compared to a C5 inhibitor alone.
All panelists (13-0) found that current evidence is not adequate to demonstrate a net health benefit for adding danicopan to a C5 inhibitor when compared to pegcetacoplan alone.

Panel members also weighed potential benefits and disadvantages beyond the direct health effects and broader contextual considerations. Voting highlighted the following as particularly important for payers and other policymakers to note:

Magnitude of the lifetime impact on individual patients of PNH;

Patients’ ability to achieve major life goals related to education, work, or family life;

Patients’ ability to manage and sustain treatment given the complexity of regimen.

ICER’s Virtual Public Meeting: Voting Results on Long-Term Value for Money

Iptacopan has been approved by the FDA (branded as Fabhalta®) and carries a list price of $550,377 per year. ICER’s analysis estimated that approximately 97% of the traditional cost-effectiveness value-based price of iptacopan comes from the cost offsets generated by eliminating the costs of the C5 inhibitor ravulizumab, which is priced at a level unaligned with its health benefits to patients. As detailed in our Value Assessment Framework, ICER applied an alternative cost-effectiveness methodology that shares the savings from cost offsets between the product innovator and the health system to calculate the health-benefit price benchmark (HBPB). Using these calculations, the HBPB for iptacopan is estimated to range between $178,000 and $180,000 annually.

Danicopan, an add-on therapy to a C5 inhibitor, has not yet been approved by the FDA, and the manufacturer has not yet announced the US price if approved. As such, a vote on long-term value was not taken. The HBPB range for danicopan is between $12,300 and $13,100 per year.

After reviewing the clinical evidence and considering the treatments’ other potential benefits, disadvantages, and contextual considerations noted above, the CTAF evaluated the long-term value of iptacopan at its current pricing:

A majority of panelists (12-1) found that iptacopan at its current pricing represents “low” long-term value for money. 

Key Policy Recommendations:

ICER’s independent assessment of value informs the critical decisions that stakeholders across the US health system need to make around pricing and coverage. Following the voting session, a policy roundtable of experts — including clinical experts, patient advocates, and representatives from US payers — convened to discuss the pricing implications and recommendations to ensure fair access. Key recommendations stemming from the roundtable discussion include:

Payers should be aware of several key issues regarding the treatment landscape for PNH: 1) patients and clinicians have become accustomed to and are satisfied with an intravenously administered C5 inhibitor as frontline therapy in treatment-naïve patients; 2) clinicians do not have prediction models or biomarkers to identify which patients treated with a C5 inhibitor will develop clinically significant extravascular hemolysis (cs-EVH) nor distinguish which switch or add-on proximal complement inhibitor for this population is best; and 3) there is a high value placed on individual shared decision making for patients choosing between a C5 inhibitor and non-intravenous treatment options.

Manufacturers who develop therapies for PNH as an add-on to one of their existing drugs on the market should consider reduced pricing for the add-on therapy to achieve fair value compared to monotherapy treatment options.

The value of novel PNH therapies should not be determined exclusively by estimates of long-term cost offsets used in traditional cost-effectiveness analyses alone, particularly when the existing standard of care is acknowledged to be priced significantly higher than reasonable cost-effective levels.

ICER’s detailed set of policy recommendations is available in the Final Evidence Report and in the standalone Policy Recommendations document.

About ICER

The Institute for Clinical and Economic Review (ICER) is an independent non-profit research institute that produces reports analyzing the evidence on the effectiveness and value of drugs and other medical services. ICER’s reports include evidence-based calculations of prices for new drugs that accurately reflect the degree of improvement expected in long-term patient outcomes, while also highlighting price levels that might contribute to unaffordable short-term cost growth for the overall health care system.

ICER’s reports incorporate extensive input from all stakeholders and are the subject of public hearings through three core programs: the California Technology Assessment Forum (CTAF), the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC), and the New England Comparative Effectiveness Public Advisory Council (New England CEPAC). These independent panels review ICER’s reports at public meetings to deliberate on the evidence and develop recommendations for how patients, clinicians, insurers, and policymakers can improve the quality and value of health care. For more information about ICER, please visit ICER’s website.